Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000797585 | SCV000937149 | uncertain significance | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 220 of the G6PD protein (p.Ile220Met). This variant is present in population databases (rs782771682, gnomAD no frequency). This missense change has been observed in individual(s) with G6PD-related symptoms (PMID: 21637675, 28028996). ClinVar contains an entry for this variant (Variation ID: 643800). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt G6PD protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Dunham Lab, |
RCV000797585 | SCV002599215 | likely pathogenic | Anemia, nonspherocytic hemolytic, due to G6PD deficiency | 2022-08-12 | criteria provided, single submitter | curation | Variant found in unrelated hemizygotes with G6PD deficiency and anemia (PS4_M, PP4). Decreased activity in red blood cells (64%) (PS3). Below expected carrier frequency in gnomAD (PM2). Post_P 0.988 (odds of pathogenicity 729.3, Prior_P 0.1). |